The syndrome is named for Heinrich Klüver and Paul Bucy, who removed the temporal lobe bilaterally in rhesus monkeys in an attempt to determine its function. This caused the monkeys to develop visual agnosia, emotional changes, altered sexual behavior, hypermetamorphosis and oral tendencies.

Though the monkeys could see, they were unable to recognize even previously familiar objects, or their use. They would examine their world with their mouths instead of their eyes ("oral tendencies") and developed a desire to explore everything ("hypermetamorphosis").

Emotionally, the monkeys became dulled, and their facial expressions and vocalizations became far less expressive. They were also less fearful of things that would have instinctively panicked them in their natural state, such as humans or snakes. Even after being attacked by a snake, they would willingly approach it again. This aspect of change was termed "placidity".

The full syndrome rarely, if ever, develops in humans. However, parts of it are often noted in patients with extensive bilateral temporal damage caused by herpes or other encephalitis and dementias of degenerative or post-traumatic etiologies.